A major strategy used to fight infection with HIV-1 is the use of protease inhibitors, which are small polypeptide derivatives. Several of these demonstrate high antiretroviral potency to HIV-1 in vitro. However, the low and variable oral bioavailability of protease inhibitors and their inability to penetrate the blood-brain barrier are significant impediments to their use in the clinic. Initially, low bioavailability was attributed to metabolism by the cytochrome P450 3A4 isoform, but recent studies have implicated another process: active extrusion out of enterocytes back into the gut lumen, mediated by the ATP-driven, drug efflux pumps. p-Glycoprotein-mediated transport at the blood-brain barrier is also implicated in the near-exclusion of protease inhibitors from the central nervous system, an important target of protease inhibitor therapy. The goal of this project is to construct a digital fluorescence microscope and computer controller with powerful deconvolution software to be used in the characterization of transport mechanisms for HIV protease inhibitors in living epithelial tissues and isolated brain capillaries. - confocal microscopy, image analysis, deonvolution, HIV drug transport